目的:评价白细胞介素-6(IL-6)抑制剂(tocilizumab)对兔骨整合过程中种植体周围细菌感染相关骨吸收的影响。
方法:共有24名男性,包括9个月的新西兰白兔,拔除了他们的两颗下颌前牙。提取后三个月,24个一体式Dentium植入物(Ø2.5mm,骨内长度为12毫米)插入前下颌骨,将家兔分为4组(每组6只)。每组采用不同的治疗方法:空白对照组(BC);仅丝线结扎(阴性对照[NC]);丝线结扎并注射盐酸米诺环素软膏(阳性对照[PC]);丝线结扎并经耳廓静脉注射托珠单抗8mg/kg(实验[EP])。八周后,动物被处死,收集样本,然后使用显微计算机断层扫描(microCT)扫描进行分析,免疫组织化学分析,和组织学分析。
结果:从microCT测量,EP组骨体积与总体积的比值(BV/TV)为67.00%±2.72%,高于其他三组(BC组的58.85%±2.43%,PC组55.72%±2.48%,NC组为36.52%±3.02%)。根据免疫组织化学分析,IL-6的表达在NC组高于BC组,PC,和EP组,但三组间无统计学差异。此外,EP组RANKL(核因子-κB受体活化因子配体)表达最低,其次是BC组,PC组,和NC组,表达最高;NC和PC组之间没有差异。组织学分析,在EP组的植入物表面发现了显著的新骨,在BC和PC组中可以看到稀疏和较少的新骨,骨吸收最严重的是NC组。
结论:Tocilizumab,IL-6的抑制剂,在预防骨整合期间由细菌感染引起的植入物周围的骨丢失方面具有一定的作用。
OBJECTIVE: To evaluate the effect of interleukin-6 (IL-6) inhibitor (tocilizumab) on bacterial infection-associated bone resorption around implants during osseointegration in rabbits.
METHODS: At total of 24 male, 9-monthold New Zealand white rabbits were included, and their two mandibular anterior teeth were extracted. Three months after extraction, 24 one-piece Dentium implants (Ø 2.5 mm, intraosseous length of 12 mm) were inserted in the anterior mandible, and the rabbits were divided into four groups (n = 6 per group). Different treatment methods were used in each group: blank control group (BC); only silk ligation (negative control [NC]); silk ligation and injection with minocycline hydrochloride ointment (positive control [PC]); and silk ligation and injection with tocilizumab at 8 mg/kg via the auricle vein (experimental [EP]). Eight weeks later, the animals were sacrificed, and samples were collected and then analyzed using microcomputed tomography (microCT) scanning, immunohistochemical analysis, and histologic analysis.
RESULTS: From the microCT measurement, the ratio of the bone volume to the total volume (BV/TV) in the EP group was 67.00% ± 2.72%, which was higher than that in the other three groups (58.85% ± 2.43% in the BC group, 55.72% ± 2.48% in the PC group, and 36.52% ± 3.02% in the NC group). From immunohistochemical analysis, the expression of IL-6 was found to be higher in the NC group than in the BC, PC, and EP groups, but there was no statistical difference between these three groups. Furthermore, the RANKL (receptor activator of nuclear factor-κB ligand) expression was the lowest in the EP group, followed by the BC group, the PC group, and the NC group, which had the highest expression; there was no difference between the NC and PC groups. Upon histologic analysis, significant new bone was found on the implant surfaces in the EP group, sparse and less new bone could be seen in the BC and PC groups, and the most serious bone resorption occurred in the NC group.
CONCLUSIONS: Tocilizumab, an inhibitor of IL-6, has a certain effect in preventing bone loss around implants caused by bacterial infection during the osseointegration period.